Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel Parkinson’s treatment strategy involves cell transplantation

26.03.2010
UCSF scientists have used a novel cell-based strategy to treat motor symptoms in rats with a disease designed to mimic Parkinson’s disease.

The strategy suggests a promising approach, the scientists say, for treating symptoms of Parkinson’s disease and other neurodegenerative diseases and disorders, including epilepsy.

The scientists transplanted embryonic neurons from fetal rats into an area of the adult rat brain known as the striatum, which integrates excitatory and inhibitory neurotransmitter signals to control movement. In Parkinson’s disease, cells that produce the neurotransmitter dopamine are damaged, and thus unable to project their communication wires, or axons, to the region. As a result, the balance of excitation and inhibition in the striatum is lost, causing the motor deficits that are a primary symptom of the disease.

In the study, the transplanted embryonic neurons migrated and integrated into the correct neural circuitry of the striatum, matured into so-called GABAergic inhibitory interneurons, and dampened the over-excitation in the region. The rats had improved motor function, as seen in their balance, speed, and length of stride during walking. Moreover, the healthy “control” rats in which the cells had been transplanted took longer strides and ran faster on a runway test.

The results, the scientists say, demonstrate that the transplanted cells, known as embryonic medial ganglionic eminence (MGE) cells, can very precisely modify the balance of excitation and inhibition in neural circuits to influence behavior. As overactive neural circuits are associated with other neurodegenerative diseases – a result of nonfunctioning or missing cells or abnormal synaptic transmission—the finding may have broad implications.

“This strategy represents a whole new approach to treating nervous system disorders,” says neurologist Arnold Kriegstein, MD, PhD, the senior author of the study and director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

The study, featured on the cover of the journal Cell Stem Cell (vol. 6, issue 3, 2010), was led by Verónica Martínez-Cerdeño, PhD, at the time a postdoctoral fellow in the Kriegstein lab, and was a collaboration involving Arturo Alvarez-Buylla, PhD, UCSF Heather and Melanie Muss Professor of Neurological Surgery and Krys Bankiewicz, MD, PhD, UCSF professor of neurological surgery.

The approach used by the team differs from another cell-based strategy for Parkinson’s disease currently being explored by other research teams. This traditional transplantation strategy involves attempting to replace the dopamine-producing cells that are lost in the disease, by grafting precursors for these cells directly in the striatum. The loss of these cells is thought to account for most of the disease’s symptoms— motor deficits, cognitive and autonomic dysfunction and disturbances in mood.

This traditional strategy has shown severe drawbacks, including that the grafted dopaminergic cells show little, if any, dispersion when grafted into the striatum, and that patients have developed disabling spontaneous movements in preliminary trials, prompting early suspension of the trials.

The ability to modify the neural circuitry of the striatum, part of a larger region known as the basal ganglia, is a function only cells can perform, says Kriegstein. The nervous system is a complex system of neural networks composed of highly individualized cells that relay electrochemical signals between regions of the brain and spinal cord at millisecond speeds, accounting for every behavior, emotion, and thought. “Each cell has its own role to play based on the circuits in which it is embedded,” he says. “It has to carry out its role at exactly the right time, with exactly the right partners, and the activity pattern changes moment by moment.

“Once MGE cells were integrated into striatal neural circuitry, they would be able to modify circuit activity, in a way no other therapies can.”

Current treatment approaches – drugs, surgery and electrical stimulation—are relatively blunt instruments, he says. Drugs, for instance, generally act indiscriminately, affecting whole areas of the nervous system, so there often are multiple side effects.

The new study findings complement two other recent UCSF studies using MGE cells to modify neural circuits. In a collaborative study among the laboratories of Scott Baraban, PhD, professor of neurological surgery; John Rubenstein, MD, PhD, professor of psychiatry, and Alvarez-Buylla, the cells were grafted into the neocortex of juvenile rodents, where they reduced the intensity and frequency of epileptic seizures. (Proceedings of the National Academy of Science, vol. 106, no. 36, 2009). Other teams are exploring this tactic, as well.

In the other study (Science, Vol. 327. no. 5969, 2010), UCSF scientists reported the first use of MGEs to broaden the period of plasticity, or capacity to change, in the mouse visual cortex. The finding, reported by the labs of Alvarez-Buylla and Michael Stryker, PhD, professor of physiology, might some day be used, they say, to create a new period of plasticity of limited duration for repairing damaged brains.

Looking ahead, the team studying MGE cells in the rat model of Parkinson’s disease plans to target a more specific sub region of the striatum, with the goal of getting a more precise effect. They also want to see if the cells could be genetically modified to produce dopamine, thus more directly addressing the biochemical changes of Parkinson’s disease, and they plan to attempt to prompt human embryonic stem cells to differentiate, or specialize, into MGE cells in the lab, with the goal of establishing a mechanism for creating a sufficient supply of the cells for clinical use.

Other co-authors of the study were Stephen C. Noctor, Ana Espinosa, Jeanele Ariza, Philip Parker, Samantha Orasji and, Marcel M. Daadi.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Jennifer O'Brien | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Health and Medicine:

nachricht The end of pneumonia? New vaccine offers hope
23.10.2017 | University at Buffalo

nachricht Scientists track ovarian cancers to site of origin: Fallopian tubes
23.10.2017 | Johns Hopkins Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>